Analysing the functions of human cytomegalovirus US28 during latent infection (360G-Wellcome-109075_Z_15_A)

Human cytomegalovirus (HCMV) is a betaherpesvirus which causes lifelong subclinical infection in healthy adults, but significant mortality and morbidity in neonates and immunocompromised individuals. Like all herpesviruses, it establishes latent infection; HCMV undergoes latency in early myeloid lineage cells. Reactivation occurs when these cells differentiate into macrophages and dendritic cells, and reactivation events in immunocompromised individuals often fail to be controlled by the host immune system causing life-threatening disease. The HCMV genome encodes a G protein coupled receptor, US28, which is expressed during both lytic and latent infection, and is essential for establishing latency. I wish to understand how US28 functions in early myeloid lineage cells to establish latency. I will be using existing proteomic analyses as a basis for investigating a number of host proteins as potential mediators and effectors of latency; a number of host proteins are modulated by US28, some of which may be implicated in immune evasion by the virus. I also aim to understand the role of G proteins in establishing latency, given the varying functions of US28 in lytic and latent infection. I hope to establish a picture of the mechanisms by which US28 manipulates the host cell to facilitate latent infection.